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1.
Can J Cardiol ; 25(2): e42-7, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19214300

ABSTRACT

BACKGROUND: C-reactive protein (CRP), a marker of inflammation, plays a role in the pathophysiology of atherosclerotic events. The relationship between CRP levels and myocardial necrosis assessed by troponin T (TnT) in patients undergoing percutaneous coronary intervention (PCI) has not been established. In addition, the long-term significance of TnT rise following PCI is not clear. OBJECTIVES: To examine the relationship between CRP and the rise in TnT levels, and evaluate the long-term prognostic implications of TnT rise following PCI. METHODS: A total of 1208 patients underwent successful nonemergent PCI. Baseline demographic characteristics, CRP and TnT levels were prospectively collected before and 12 h to 18 h following PCI. Long-term follow-up data over two years were available. RESULTS: Among the patients studied (mean age 62 years), 64% presented with acute coronary syndrome. A PCI procedure was associated with a significant increase in TnT levels (higher than 0.1 microg/L) in 238 patients (20%). Multivariate logistic regression identified presentation with acute coronary syndrome or myocardial infarction, no statin use at the time of the procedure, increased CRP and increasing length of stent as independent predictors of TnT rise following PCI. Periprocedural TnT rise was not associated with adverse events in follow-up examinations (OR 1.09, 95% CI 0.73 to 1.65). CONCLUSIONS: Myocardial necrosis commonly occurred in otherwise successful PCI and was particularly prevalent in the proinflammatory milieu of a recent myocardial infarction. This response was blunted with statin therapy. However, there was no long-term adverse sequelae of these troponin rises following otherwise uncomplicated PCI.


Subject(s)
Angioplasty, Balloon, Coronary/adverse effects , C-Reactive Protein/metabolism , Inflammation/physiopathology , Myocardial Infarction/blood , Myocardial Infarction/therapy , Myocardium/pathology , Troponin T/blood , Acute Coronary Syndrome/blood , Anticholesteremic Agents/therapeutic use , Biomarkers/blood , Confidence Intervals , Female , Follow-Up Studies , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation/drug therapy , Logistic Models , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/physiopathology , Myocardial Infarction/prevention & control , Odds Ratio , Prognosis , Time Factors
2.
Obes Res Clin Pract ; 3(1): 1-52, 2009 Mar.
Article in English | MEDLINE | ID: mdl-24345536

ABSTRACT

BACKGROUND: Obesity is an independent risk factor for cardiovascular disease. Endothelial dysfunction assessed in the peripheral circulation is associated with obesity, however, little is known if this association also exists in the coronary circulation. METHODS: Stable patients with coronary artery disease were evaluated. Baseline characteristics were evaluated, including assessment of body mass index [(BMI), kg/m(2)]. Coronary diameter (quantitative coronary angiography) and blood flow (0.014 in. Doppler Flo-wire) were measured at baseline and in response to intracoronary acetylcholine (10(-7) and 10(-6) M) to evaluate endothelial dependent effects with endothelial independent effects evaluated in response to intracoronary nitroglycerin and adenosine. The cohort was divided into tertiles around BMI values, i.e. normal weight (BMI < 25), overweight (BMI 25-29.9) and obese (BMI ≥ 30) groups. RESULTS: 83 patients were evaluated, with 20 patients in the normal weight (BMI 22.6 ± 0.3 kg/m(2)), 40 subjects in the overweight (BMI 27.3 ± 0.2 kg/m(2)) and 23 in the obese (BMI 34.3 ± 0.3 kg/m(2)) groups. A significant difference was seen in the primary endpoint of Ach mediated % change in coronary blood flow between the normal (101 ± 28%) and the obese (37 ± 15%) groups (p = 0.04). No significant difference was observed in epicardial constrictor response to acetylcholine across these three groups of patients. CONCLUSIONS: In a cohort of subjects with coronary artery disease, patients with a high BMI had associated impaired microvascular coronary endothelial dependent function.

3.
Cardiovasc Res ; 76(3): 539-46, 2007 Dec 01.
Article in English | MEDLINE | ID: mdl-17689509

ABSTRACT

OBJECTIVES: Reduced nitric oxide (NO) bioavailability is a key mechanism in the development of endothelial dysfunction. The NO synthase cofactor, tetrahydrobiopterin (BH4), increases NO availability, yet its effect in the human coronary circulation, particularly following PCI, remains uncertain. This study was designed to evaluate the effects of intracoronary BH4 in human coronary arteries with non-critical coronary artery disease or following percutaneous coronary intervention (PCI). METHODS: The study group consisted of 57 stable patients, 10 of which were controls. Active drug was administered in 47 patients, with either de novo non-critical coronary disease (non-stent group; n=25) or following PCI (stent group; n=22). Coronary blood flow (CBF) was measured (0.014-inch Doppler flow wire) in each of these groups in response to sequential intracoronary infusions of acetylcholine (Ach, 10(-7) & 10(-6) M), BH4 (250 microg/min & 500 microg/min) and a co-infusion of BH4 (500 microg/min) and Ach (10(-7) & 10(-6) M). The primary endpoint evaluated the % change in CBF to Ach compared to co-infusion of Ach and BH4. RESULTS: Mean age was 60+/-10 years (M 45:F 12). Regarding the primary hypothesis, no difference was observed between Ach response compared to co-infusion of BH4 and Ach in the % change in CBF in either the non-stent group (Ach 97+/-122%, Ach/BH4 87+/-95%) or the stent group (Ach 77+/-105%, Ach/BH4 55+/-97%). CONCLUSIONS: In native non-critical coronary artery disease or following PCI, coronary microvascular endothelial function is not improved by co-administration of Ach and BH4.


Subject(s)
Atherosclerosis/physiopathology , Biopterins/analogs & derivatives , Coronary Vessels/physiopathology , Endothelium, Vascular/physiopathology , Regional Blood Flow/drug effects , Acetylcholine/pharmacology , Acetylcholine/therapeutic use , Aged , Angioplasty, Balloon, Coronary , Atherosclerosis/pathology , Atherosclerosis/therapy , Biopterins/pharmacology , Biopterins/therapeutic use , Combined Modality Therapy , Coronary Vessels/drug effects , Coronary Vessels/pathology , Drug Therapy, Combination , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Female , Humans , Male , Middle Aged , Regional Blood Flow/physiology , Stents , Treatment Outcome , Vasodilator Agents/pharmacology , Vasodilator Agents/therapeutic use
4.
Heart Lung Circ ; 15(5): 300-5, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16877042

ABSTRACT

BACKGROUND: In this new-era of drug-eluting stents (DES) the impact of symptomatic in-stent restenosis (ISR) is diminishing. However, world wide bare-metal stents remain widely used and therefore, it is imperative to establish a simple and effective form of treatment. The objective of this registry database was to evaluate the 'real-world' effectiveness of DES for the treatment of symptomatic bare-metal stent ISR. METHODS: All patients presenting with symptomatic ISR were evaluated between February 2003 and February 2005. Patients had 9-month angiographic follow-up with primary endpoint evaluation of binary restenosis (>50%). Secondary endpoints included in-segment late loss, target lesion revascularization (TLR) and the difference in late loss between sirolimus (n=23) and paciltaxel (n=36) eluting stents. RESULTS: Fifty eight patients with fifty nine ISR lesions were evaluated, 36% of patients had diabetes mellitus. All procedures were performed safely with no adverse peri-procedural events documented. At 9-month follow-up the median in-segment late loss was 0.24 mm (IQR 0.1, 0.53), with a binary restenosis rate of 17%. At long-term follow-up greater than 1 year, the incidence of TLR was 10%. No difference in the angiographic parameter of in-segment late loss was seen between the sirolimus and paclitaxel-eluting stents. CONCLUSIONS: In this cohort of patients with long-term angiographic and clinical follow-up, DES is an effective and safe treatment for symptomatic bare-metal stent ISR.


Subject(s)
Blood Vessel Prosthesis Implantation/instrumentation , Coated Materials, Biocompatible , Coronary Restenosis/surgery , Paclitaxel/pharmacology , Sirolimus/pharmacology , Stents , Antineoplastic Agents, Phytogenic/pharmacology , Coronary Angiography , Coronary Restenosis/diagnostic imaging , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/pharmacology , Male , Middle Aged , Prosthesis Failure , Reoperation , Retrospective Studies , Time Factors , Treatment Outcome
5.
Am Heart J ; 151(2): 529.e1-529.e6, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16442926

ABSTRACT

BACKGROUND: Myocardial ischemia is one of several potential causes of increased QT dispersion (QTd) in patients with nonacute total coronary artery occlusions (TCOs). We sought to assess the effect of percutaneous revascularization (PCI) of TCO on QTd and the relationship between QTd and long-term vessel patency. METHODS: Seventy patients enrolled in the TOSCA were analyzed. Patients were undergoing PCI of a TCO > 72 hours' duration. Two independent reviewers measured QTd from electrocardiograms done immediately before PCI (PRE), 12 to 18 hours after PCI (POST), and then at 6 months (6M). Follow-up angiography was performed at 6 months. RESULTS: Mean QTd decreased from PRE (77 +/- 29 milliseconds) to POST (66 +/- 26 milliseconds, P < .001) and 6M (65 +/- 25 milliseconds, P < .001). Patients with the same or longer QTd at 6 months compared with POST (POST < or = 6M) had significantly higher risk of failed target-vessel patency (odds ratio 10.3, 95% CI 1.24-84.8) than patients with QTd reduction at 6M versus POST values. CONCLUSION: Revascularization of TCO resulted in a decrease in QTd, which was sustained at 6M. This suggests that PCI to a TCO has a beneficial effect on stabilization of the underlying ischemic substrate. Furthermore, absence of QTd reduction at 6M versus POST was associated with increased risk of failed target-vessel patency.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Disease/physiopathology , Coronary Disease/therapy , Coronary Angiography , Coronary Disease/diagnostic imaging , Electrocardiography , Humans , Middle Aged , Myocardial Infarction/physiopathology , Time Factors
6.
Am Heart J ; 151(1): 175, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16368313

ABSTRACT

BACKGROUND: Direct comparison of low-molecular-weight heparin, dalteparin, with unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) is limited. This study examined the relative effects of dalteparin and UFH on coagulation and angiographic and clinical indices during PCI. METHODS: This was a double-blind randomized study, stratified by planned glycoprotein IIb/IIIa inhibitor use. Both UFH and dalteparin were administered as an intra-arterial bolus immediately before PCI. RESULTS: All randomized patients received the assigned study drug and underwent PCI. Mean activated clotting time levels were 344 seconds for UFH and 234 seconds for dalteparin (P < .0001). Anti-factor Xa levels were higher for dalteparin at 30 minutes (UFH 1.3 IU/mL vs dalteparin 1.7 IU/mL, P = .005)) and at 4 hours (UFH 0.27 IU/mL vs dalteparin 0.69 IU/mL, P < .0001). Angiographic success was > 90% in both groups, and angiographic complications were similar (UFH 2.5% vs dalteparin 3.8%). The composite of death, myocardial infarction, target vessel revascularization, or bailout glycoprotein IIb/IIIa at hospital discharge was 13.7% in the UFH group and 13.1% in the dalteparin group (P = not significant). There were 2 major bleedings requiring transfusion, both occurring in the UFH group. CONCLUSIONS: This study suggests that a single intra-arterial bolus of low-molecular-weight heparin without monitoring is feasible and warrants further investigation as an alternative to UFH during PCI.


Subject(s)
Angioplasty, Balloon, Coronary , Anticoagulants/therapeutic use , Dalteparin/therapeutic use , Double-Blind Method , Female , Heparin/therapeutic use , Humans , Intraoperative Care , Male , Middle Aged , Pilot Projects
7.
Am J Cardiol ; 95(10): 1170-4, 2005 May 15.
Article in English | MEDLINE | ID: mdl-15877988

ABSTRACT

Coronary disease or its risk factors has been reported to attenuate basal nitric oxide (NO) activity. Intravascular ultrasound was used in the present study to better understand this relation. Basal and stimulated NO activities were assessed in 53 stable subjects. Coronary diameter and velocity (0.014-inch Doppler wire) were measured at baseline and after intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl-l-arginine, acetylcholine (10(-6) M), nitroglycerin (200 microg), and adenosine (24 microg). Intimal thickening was quantified with intravascular ultrasound. N(G)-monomethyl-l-arginine resulted in significant decreases in coronary blood flow (-14 +/- 48%), proximal coronary diameter (-10 +/- 18%), and distal coronary diameter (-10 +/- 9%, all p values <0.0001). Basal NO activity was unrelated to the presence of coronary disease as assessed by angiography and the burden of atherosclerosis as assessed by intravascular ultrasound. Conversely, stimulated NO activity correlated inversely with burden of coronary atherosclerosis (p <0.05). Basal NO activity is relatively preserved in patients who have moderate coronary disease and is not related to the degree of atherosclerosis as assessed by intravascular ultrasound. This is in contradistinction to the impairment of stimulated NO activity in the coronary circulation that characterizes atherosclerosis.


Subject(s)
Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/physiopathology , Nitric Oxide/physiology , Adenosine , Blood Flow Velocity , Coronary Angiography , Coronary Circulation , Enzyme Inhibitors , Female , Humans , Laser-Doppler Flowmetry , Male , Middle Aged , Nitric Oxide Synthase/antagonists & inhibitors , Nitroglycerin , Pulsatile Flow , Severity of Illness Index , Ultrasonography , omega-N-Methylarginine
8.
Circulation ; 111(11): 1390-7, 2005 Mar 22.
Article in English | MEDLINE | ID: mdl-15781750

ABSTRACT

BACKGROUND: Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to standard therapies for the prevention of venous thrombosis. We performed a randomized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention (PCI) setting. METHODS AND RESULTS: A total of 350 patients undergoing elective or urgent PCI were randomized in a blinded manner to receive unfractionated heparin (UFH), 2.5 mg fondaparinux IV, or 5.0 mg fondaparinux IV. Randomization was stratified for planned or no planned use of glycoprotein (GP) IIb/IIIa antagonists. The primary safety outcome was total bleeding, which was a combination of major and minor bleeding events. The incidence of total bleeding was 7.7% in the UFH group and 6.4% in the combined fondaparinux groups (hazard ratio, 0.81; 95% confidence interval, 0.35 to 1.84; P=0.61). Bleeding was less common in the 2.5-mg fondaparinux group compared with the 5-mg fondaparinux group (3.4% versus 9.6%, P=0.06). The composite efficacy outcome of all-cause mortality, myocardial infarction, urgent revascularization, or need for a bailout GPIIb/IIIa antagonist was 6.0% in the UFH group and 6.0% in the fondaparinux group, with no significant difference in efficacy among the fondaparinux doses compared with UFH. Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation, as measured by prothrombin fragment F1.2 (P=0.02). CONCLUSIONS: In this pilot study of patients undergoing contemporary PCI, factor Xa inhibition with the synthetic anticoagulant fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes. These data form the basis for further evaluation of fondaparinux in arterial thrombosis.


Subject(s)
Angioplasty, Balloon, Coronary , Anticoagulants/therapeutic use , Heparin/therapeutic use , Polysaccharides/therapeutic use , Aged , Anticoagulants/adverse effects , Emergencies , Factor Xa Inhibitors , Feasibility Studies , Female , Fondaparinux , Hemorrhage/etiology , Heparin/adverse effects , Hospital Mortality , Humans , Male , Middle Aged , Myocardial Infarction/epidemiology , Myocardial Revascularization/statistics & numerical data , Pilot Projects , Polysaccharides/adverse effects , Single-Blind Method , Stents , Treatment Outcome
9.
Am J Cardiol ; 93(6): 750-3, 2004 Mar 15.
Article in English | MEDLINE | ID: mdl-15019884

ABSTRACT

The objectives of this study were to investigate the incidence, predictors, and clinical significance of isolated postprocedural troponin-I elevations in a consecutive series of patients who underwent percutaneous coronary intervention. We observed, in a series of 1,128 patients, that isolated troponin-I elevations without concomitant creatine kinase elevations occurred in 17% of patients after percutaneous coronary intervention, and that even troponin-I elevations 5 times above the upper limit of normal did not predict events after hospital discharge.


Subject(s)
Creatine Kinase/blood , Myocardial Infarction/blood , Myocardial Infarction/mortality , Troponin I/blood , Angioplasty, Balloon, Coronary , Biomarkers/blood , Disease-Free Survival , Female , Humans , Incidence , Male , Middle Aged , Myocardial Infarction/epidemiology , Myocardial Infarction/etiology , Myocardial Infarction/therapy , Ontario/epidemiology , Postoperative Period , Predictive Value of Tests , Prognosis , Survival Analysis
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